Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

Abstract

BackgroundNon-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited.Patients and methodsWe retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed.ResultsWe included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.ConclusionsOur results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.

Consensus for HER2 alterations testing in non-small-cell lung cancer

“… 43 A multicenter retrospective study included metastatic NSCLC patients harboring HER2 alterations administered afatinib, revealing an ORR of 33%, an mPFS of 3.3 months and a median OS of 13.4 months in HER2 amplification. 56 These results indicate that effective targeted drugs for NSCLC with HER2 amplification and/or overexpression need to be further investigated.…”

Pyrotinib for HER2-amplified non-small cell lung cancer patient after progression to Afatinib: a case report

“…The efficacy of afatinib in NSCLC harboring HER2alterations is controversial [10][11][12], with no prospective trials for the HER2-amplificated population. HER2 amplification is considered to be one of the mechanisms of EGFR-TKIs resistance [13,14], which is confirmed in osimertinib (the third-generation EGFR-TKI) [15].…”

Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non–Small-Cell Lung Cancer

“…Using the reference human genome hg19 Burrows-Wheeler Aligner (v0.7.12), paired sample raw data from the FFPE sample and respective normal tissue control were mapped. 18,21 Polymerase chain reaction duplicate reads were removed, and sequence metrics were collected using Picard (v1.130) and SAMtools (v1.1.19), respectively.Somatic single-nucleotide variants were detected using an R package developed in-house for variant detection on the basis of a binomial test. Indel detection was achieved by local realignment.…”

“…Using the reference human genome hg19 Burrows-Wheeler Aligner (v0.7.12), paired sample raw data from the FFPE sample and respective normal tissue control were mapped. 18,21 Polymerase chain reaction duplicate reads were removed, and sequence metrics were collected using Picard (v1.130) and SAMtools (v1. 1.19), respectively.…”